AVENIR I demonstrated efficacy of azithromycin MDA targeted to children 1-59 over 1-11 months in July 2023, thus this trial was stopped before outcomes were collected so Niger could expand the program nationally to include children 1-59 months.

The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality settings. The proposed trial aims to demonstrate and evaluate large-scale implementation of azithromycin to children aged 1-11 months old in the context of a programmatic setting while monitoring mortality and resistance antimicrobial resistance.

In the Programmatic Trial, community health centers (also known as "CSIs" or "Centres de Santé Intégrés") will be randomized to one of two arms: 1) programmatic azithro 1-11: biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers or 2) no intervention: no distribution of azithromycin. A total of 2,490 communities within selected CSIs will be included .

All communities in both arms receive routine health services offered by community health workers working for the Niger Ministry of Health's community health program.

Mortality will be monitored through birth histories. Mortality and morbidity will also be monitored using routinely collected community and clinic visit data. Antimicrobial resistance will be monitored in a subset of eligible CSIs.

Intervention

At the community-level, eligibility includes:

Inclusion Criteria:

• Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
• Distinguishable from neighboring communities
• Verbal consent of community leader(s)

Exclusion criteria:

• Inaccessible or unsafe for study team
• "Quartier" designation on national census

At the individual-level, eligibility includes:

Inclusion criteria:

• Age 1-11 months
• Primary residence in a study community
• Verbal consent of caregiver/guardian for study participation

Exclusion criteria:

• Known allergy to macrolides

Population-based sample collections

At the community-level, eligibility includes:

Inclusion criteria:

• Location in study region
• Distinguishable from neighboring communities
• Verbal consent of community leader(s)

Exclusion criteria:

• Inaccessible or unsafe for study team
• Included in MORDOR trials
• Not randomly selected

At the individual-level, eligibility includes:

Inclusion criteria:

• Age 1-59 months or 7-12 years or caregiver/guardian of a child eligible for treatment
• Primary residence in a study community selected for sample collections
• Verbal consent of caregiver/guardian for study participation

Exclusion criteria:

• Not on list of randomly selected participants from the census

De-identified data underlying outcomes publications will be made publicly available.

Individual participant data will be made available after publication of the outcomes and will be made available indefinitely.

Once made available, the data will be open access.

Inclusion criteria includes: age 1-59 months, primary residence in a study community, verbal consent of caregiver/guardian of children for study participation, weight ≥ 3.0 kg.

Children were enrolled for participation. not guardians.

The No Intervention arm data was not collected given the pragmatic design of the trial; therefore, the Programmatic Azithro 1-11 data was used to estimate the No Intervention population (33,953).

Reporting adverse event data began with the first round of treatment through the last round of treatment. If a child experiences an adverse event within 28 days of treatment, it was reported. time frame for reporting was 12 months

According to Pfizer, a serious adverse event (SAE) is any adverse event that: results in death, Is life-threatening (i.e., causes an immediate risk of death), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity. Or that is considered to be: an important medical event.

Participants, investigators, and program implementers will not be actively masked from the study arm allocation given that no placebo will be used. Outcome assessors and data analysts will be masked.